Hypothalamic expression of lapp is markedly decreased in ob/ob mice and normalized by exogenous leptin.

In slices, amylin and leptin had similar electrophysiologic effects on lateral hypothalamic leptin receptor ObRb-expressing neurons, while the amylin antagonist AC187 inhibited their activity and blunted the effect of leptin.

Finally, i.c.v. infusion of AC187 acutely reduced the anorectic effects of leptin. These data show that hypothalamic amylin is transcriptionally regulated by leptin, that it can act directly on ObRb neurons in concert with leptin, and that it regulates feeding.

These findings provide a potential mechanism for the increased efficacy of a metreleptin/pramlintide combination therapy for obesity.